The present invention relates to the use of compounds to affect the growth of certain bacterial species. More specifically, the present invention relates to the use of tetrahydroiso alpha acids or hexahydro beta acids at concentrations effective to kill, inhibit, or otherwise control the growth or proliferation of Staphylococcus aureus without preventing the growth of Lactobacillus. The inhibition of S. aureus in accordance with the present invention thus provides useful products, compositions and methods for treating the diseases associated with S. aureus infections and infestations, i.e. toxic shock syndrome, without disrupting the normal bacterial flora in the area of its application.
A commonly known disease caused by S. aureus is toxic shock syndrome (TSS). TSS is a severe, toxin-induced disease arising from the exposure to the S. aureus toxin called toxic shock syndrome toxin-1 (TSST-1) (Iandolo, Ann. Rev. of Micro. 43:275–402, 1989). The disease is characterized by a sudden onset of symptoms, including high fever, chills, rash, vomiting or diarrhea, and a rapid drop in blood pressure leading to shock.
Toxic shock syndrome has been reported to occur in both men and women of all ages, with approximately two cases occurring annually per 10,000 people. TSS, however, is most commonly seen in menstruating women in whom the primary site of infection is the vagina. Epidemiological evidence especially suggests that women who use highly absorbent tampons incur an increased risk for developing the disease as the highly absorbent tampon serves as an suitable environment for S. aureus growth. TSS has also been reported to occur in infants, children, men, and non-menstruating women, but at a lower frequency. These cases are generally not associated with the use of tampons, but result from skin wounds or infections in other parts of the body. The use of barrier contraceptives has also been implicated as another risk factor.
Because of the sudden onset of the disease, persons suffering from TSS may not receive appropriate medical intervention before serious complications result. Such complications may include kidney failure, heart failure, liver failure and profound shock. Accordingly, there is a very strong emphasis on disease prevention. For example, women are cautioned against using high absorbency tampons. However, many women are not willing to sacrifice the comfort and convenience of using high absorbency tampons for what they perceive to be a remote risk of developing TSS. Therefore, considerable effort has been directed toward developing new tampons capable of reducing the risk of contracting TSS as compared to conventional tampons.
Various approaches for preventing toxic shock syndrome from tampon use have been advanced. One such method includes incorporating bactericidal or bacteriostatic agents (i.e., antibiotics or phenol) into the tampon to inhibit S. aureus growth. Other methods include the incorporation of agents which prevent the production of TSST-1 or inactivate TSST-1. For example, U.S. Pat. No. 4,405,323 discloses the incorporation of an antibacterial agent, such as povione-iodine, mercury, zinc, penicillin, erythromycin, and nitrofurazone, within a tampon to prevent TSS. U.S. Pat. No. 4,431,427 discloses the incorporation of a water-soluble acid (i.e., citric, glycolic, malic, tartaric, or lactic acid) in a tampon at an amount sufficient to maintain a pH of 4.5 or less in the fluids absorbed by the tampon so as to inhibit the growth of pathogenic bacteria. PCT publication WO 86/05388 discloses that the inclusion of a nontoxic divalent cation, such as magnesium, barium, calcium, strontium, or the like, in an absorptive pad has the effect of inhibiting the production of TSST-1 by S. aureus. U.S. Pat. No. 4,585,792 discloses that L-ascorbic acid may be delivered on a tampon to the vaginal area so as to inactivate the toxins associated with TSS. U.S. Pat. No. 5,389,374 discloses that the production of S. aureus enterotoxins can be inhibited by exposing the bacterium to an absorbent material treated with either a mono- or diester of apolyhydric aliphatic alcohol.
Although the use of some of these approaches have proven effective in inhibiting the growth of S. aureus and TSS, their use may also be problematic. For example, exposing a bacterial population to antibiotics may select for antibiotic resistant mutants, and decrease the efficacy of the antibiotic in treating future infections. In addition, the inclusion of conventional antibiotics will likely result in a considerable increase in cost to the consumer. Moreover, the use of antibiotics or other bactericidal or bacteriostatic agents may have the undesirable effect of disrupting the normal bacterial flora present in their area of application, ultimately resulting in the onset of other bacterial infections and diseases. For example. Lactobacillus is one of the predominant bacteria among normal vaginal flora. The administration of a compound which inhibits Lactobacillus may also have the added affect of promoting the establishment of other, less desirable microorganisms which are also present in the vagina. For instance, a low number of Candida albicans may be present in the vagina of many healthy asymptomatic women. The administration of a compound which inhibits the growth of Lactobacillus may also have the added affect of allowing C. albicans to grow and predominate, resulting in a yeast infection.
It would be advantageous, therefore, to have a method for preventing TSS which does not affect normal bacterial flora, and does not allow for the selection of antibiotic resistant bacteria, and does not result in a substantial increase in the overall cost to the consumer. In particular, what is needed is a relatively inexpensive method for inhibiting the growth of S. aureus without preventing the growth of Lactobacillus or other normal microflora.